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Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cytokines are key modulators of T cell biology, but their influence can be attenuated by suppressors of cytokine signaling (SOCS), a family of proteins consisting of eight members, SOCS1-7 and CIS. SOCS proteins regulate cytokine signals that control the polarization of CD4(+) T cells into Th1, Th2, Th17, and T regulatory cell lineages, the maturation of CD8(+) T cells from naïve to "stem-cell memory" (Tscm), central memory (Tcm), and effector memory (Tem) states, and the activation of these lymphocytes. Understanding how SOCS family members regulate T cell maturation, differentiation, and function might prove cri...
Source: Trends in Immunology - October 29, 2009 Category: Allergy & Immunology Authors: Palmer DC, Restifo NP Tags: Trends Immunol Source Type: journals

T cell-microglial dialogue in Parkinson's disease and amyotrophic lateral sclerosis: are we listening?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Neuroinflammation is a pathological hallmark in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), and is characterized by activated microglia and infiltrating T cells at sites of neuronal injury. In PD and ALS, neurons do not die alone; neuronal injury is non-cell-autonomous and depends on a well-orchestrated dialogue in which neuronally secreted misfolded proteins activate microglia and initiate a self-propagating cycle of neurotoxicity. Diverse populations and phenotypes of CD4(+) T cells crosstalk with microglia, and depending on their activation status, influence this dialogue and promote neuroprote...
Source: Trends in Immunology - October 29, 2009 Category: Allergy & Immunology Authors: Appel SH, Beers DR, Henkel JS Tags: Trends Immunol Source Type: journals

Innate immune responses to influenza A H5N1: friend or foe?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Avian influenza A H5N1 remains unusual in its virulence for humans. Although infection of humans remains inefficient, many of those with H5N1 disease have a rapidly progressing viral pneumonia that leads to acute respiratory distress syndrome and death, but its pathogenesis remains an enigma. Comparison of the virology and pathogenesis of human seasonal influenza viruses (H3N2 and H1N1) and H5N1 in patients, animal models and relevant primary human cell cultures is instructive. Although the direct effects of viral replication and differences in the tropism of the virus for cells in the lower respiratory tract clearly c...
Source: Trends in Immunology - October 26, 2009 Category: Allergy & Immunology Authors: Peiris JS, Cheung CY, Leung CY, Nicholls JM Tags: Trends Immunol Source Type: journals

Monocytes and gammadelta T cells: close encounters in microbial infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
gammadelta T cells comprise an evolutionarily conserved yet poorly understood subset of T cells. Numerous features place these unconventional lymphocytes at the branching point between antigen-presenting cells and natural killer cells of the innate immune system and major-histocompatibility-complex-restricted alphabeta T cells of the adaptive immune system. We propose a role for human Vgamma9/Vdelta2 T cells in the generation of monocyte-derived inflammatory dendritic cells during infection. Our model incorporates the peculiar innate-like specificity of Vgamma9/Vdelta2 T cells for the microbial metabolite (E)-4-hydroxy...
Source: Trends in Immunology - October 23, 2009 Category: Allergy & Immunology Authors: Eberl M, Moser B Tags: Trends Immunol Source Type: journals

Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Immunity in the newborn is characterized by minimal T helper (Th)1 function but an excess of Th2 activity. Since Th1 lymphocytes are important to counter microbes and Th2 cells favor allergies, the newborn faces susceptibility to microbial infections and allergic reactions. Delayed maturation of certain dendritic cells leads to limited interleukin (IL)-12 production during the neonatal period. The Th2 cytokine locus of neonatal CD4(+) T cells is poised epigenetically for rapid and robust production of IL-4 and IL-13. Together, these circumstances lead to efficient differentiation of Th2 cells and the expression of an I...
Source: Trends in Immunology - October 18, 2009 Category: Allergy & Immunology Authors: Zaghouani H, Hoeman CM, Adkins B Tags: Trends Immunol Source Type: journals

Lymph node tumor metastases: more susceptible than primary tumors to CD8(+) T-cell immune destruction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hematopoietic cells, and more particularly, dendritic cells are so called "professional" antigen-presenting cells, which prime CD8(+) T-cell responses. They achieve this by taking up antigens and presenting them to CD8(+) T cells in the draining lymph nodes. This process is called cross-presentation (XP). For most developing tumors, XP of tumor antigens results in CD8(+) T-cell tolerance. In addition to XP, direct presentation by any kind of cell can also occur in lymph nodes. We discuss here how a non-hematopoietic cell can efficiently prime CD8(+) T cells by direct presentation in lymph nodes. Such a T-cell activatio...
Source: Trends in Immunology - October 15, 2009 Category: Allergy & Immunology Authors: Contassot E, Preynat-Seauve O, French L, Huard B Tags: Trends Immunol Source Type: journals

Can cells and biomaterials in therapeutic medicine be shielded from innate immune recognition?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biomaterials (e.g. polymers, metals, or ceramics), cell and cell cluster (e.g. pancreatic islets) transplantation are beginning to offer novel treatment modalities for some otherwise intractable diseases. The innate immune system is involved in incompatibility reactions that occur when biomaterials or cells are introduced into the blood circulation. In particular, the complement, coagulation and contact systems are involved in the recognition of biomaterials and cells, eliciting activation of platelets and leukocytes. Such treatments are associated with anaphylactoid and thrombotic reactions, inflammation, and rejectio...
Source: Trends in Immunology - October 14, 2009 Category: Allergy & Immunology Authors: Nilsson B, Korsgren O, Lambris JD, Ekdahl KN Tags: Trends Immunol Source Type: journals

T cell receptor triggering by force.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Antigen recognition through the interaction between the T cell receptor (TCR) and peptide presented by major histocompatibility complex (pMHC) is the first step in T cell-mediated immune responses. How this interaction triggers TCR signalling that leads to T cell activation is still unclear. Taking into account the mechanical stress exerted on the pMHC-TCR interaction at the dynamic interface between T cells and antigen presenting cells (APCs), we propose the so-called receptor deformation model of TCR triggering. In this model, TCR conformational change induced by mechanical forces initiates TCR signalling. The recept...
Source: Trends in Immunology - October 14, 2009 Category: Allergy & Immunology Authors: Ma Z, Finkel TH Tags: Trends Immunol Source Type: journals

The need to identify myeloid dendritic cell progenitors in human blood.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dendritic cells (DC) are professional phagocytes possessing a unique ability to sense perturbations in the tissue microenvironment and promote adaptive immune responses, whilst maintaining immunological tolerance. Mouse myeloid DC progenitors with the ability to migrate through the blood and replenish the DC pool have been identified in bone marrow but the ontogeny of human DC is poorly understood. Access to lymphoid tissues for human DC isolation is severely limited and researchers have resorted to the use of in vitro derivation systems in attempts to understand DC development, which may result in misleading conclusio...
Source: Trends in Immunology - October 13, 2009 Category: Allergy & Immunology Authors: Mortellaro A, Wong SC, Fric J, Ricciardi-Castagnoli P Tags: Trends Immunol Source Type: journals

Innate and adaptive immune responses regulated by glycogen synthase kinase-3 (GSK3).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In just a few years, the view of glycogen synthase kinase-3 (GSK3) has been transformed from an obscure enzyme seldom encountered in the immune literature to one implicated in an improbably large number of roles. GSK3 is a crucial regulator of the balance between pro- and anti-inflammatory cytokine production in both the periphery and the central nervous system, so that GSK3 inhibitors such as lithium can diminish inflammation. GSK3 influences T-cell proliferation, differentiation and survival. Many effects stem from GSK3 regulation of critical transcription factors, such as NF-kappaB, NFAT and STATs. These discoveries...
Source: Trends in Immunology - October 13, 2009 Category: Allergy & Immunology Authors: Beurel E, Michalek SM, Jope RS Tags: Trends Immunol Source Type: journals

CD24-Siglec G/10 discriminates danger- from pathogen-associated molecular patterns.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is now well accepted that the innate immune system recognizes both damage (or danger)- and pathogen-associated molecular patterns (DAMP and PAMP, respectively) through pattern recognition receptors, such as Toll-like receptors (TLR) and/or Nod-like receptors (NLR). Less clear are whether and how the response to PAMP and DAMP are regulated differentially. The answers may reveal whether the primary goal of the immune system is to defend against infections or to alert the host of tissue injuries. We demonstrated recently that the host response to DAMP is controlled by a DAMP-CD24-Siglec axis. Here we propose a key role...
Source: Trends in Immunology - September 25, 2009 Category: Allergy & Immunology Authors: Liu Y, Chen GY, Zheng P Tags: Trends Immunol Source Type: journals

Psoriasis - as an autoimmune disease caused by molecular mimicry.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Psoriasis is strongly associated with streptococcal throat infection, and patients have increased occurrence of such infections. Psoriatic lesional T cells are oligoclonal, and T cells recognizing determinants common to streptococcal M-protein and keratin have been detected in patients' blood. We propose that CD8(+) T cells in psoriatic epidermis respond mainly to such determinants, whereas CD4(+) T cells in the dermis preferentially recognize determinants on the streptococcal peptidoglycan that might itself act as an adjuvant. The streptococcal association might reflect the concurrence of superantigen production promo...
Source: Trends in Immunology - September 22, 2009 Category: Allergy & Immunology Authors: Valdimarsson H, Thorleifsdottir RH, Sigurdardottir SL, Gudjonsson JE, Johnston A Tags: Trends Immunol Source Type: journals

Endotoxin tolerance: new mechanisms, molecules and clinical significance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prior exposure of innate immune cells like monocytes/macrophages to minute amounts of endotoxin cause them to become refractory to subsequent endotoxin challenge, a phenomenon called "endotoxin tolerance". Clinically, this state is associated with monocytes/macrophages in sepsis patients where they contribute to "immunosuppression" and mortality. The molecular mechanisms underlying endotoxin tolerance remain elusive. The recent appreciation of inflammation as a self-regulating process, the relative contribution of MyD88 versus TRIF signaling pathways in inducing activation or tolerance, plasticity of NF-kappaB function...
Source: Trends in Immunology - September 22, 2009 Category: Allergy & Immunology Authors: Biswas SK, Lopez-Collazo E Tags: Trends Immunol Source Type: journals

Thymic epithelial cells: the multi-tasking framework of the T cell "cradle"Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The thymus provides the anatomical "cradle" that fosters developing thymocytes. Thymic epithelial cells (TECs) are specialized cellular components that may be viewed as a multifunctional "frame" to nurture distinct stages of thymopoiesis. A symbiotic relationship between TECs and thymocytes exists because reciprocal interactions are required to achieve complete maturation of both cell types. Here, we propose that crucial instructive signals delivered by developing thymocytes negatively regulate functional attributes of immature TECs (including the expression of Delta-like 4 (DLL4) and interleukin-7 (IL-7)) that are req...
Source: Trends in Immunology - September 22, 2009 Category: Allergy & Immunology Authors: Alves NL, Huntington ND, Rodewald HR, Di Santo JP Tags: Trends Immunol Source Type: journals

Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Many diseases have an inflammatory component, where neutrophil interactions with the vascular endothelium lead to barrier dysfunction and increased permeability. Neutrophils increase permeability through secreted products such as the chemokines CXCL1, 2, 3, and 8, through adhesion-dependent processes involving beta(2) integrins interacting with endothelial ICAM-1, and through combinations where beta(2) integrin engagement leads to degranulation and secretion of heparin-binding protein. Some neutrophil products, such as arachidonic acid or the leukotriene LTA4, are further processed by endothelial enzymes via transcellu...
Source: Trends in Immunology - September 21, 2009 Category: Allergy & Immunology Authors: Distasi MR, Ley K Tags: Trends Immunol Source Type: journals

Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Polymorphonuclear neutrophils (PMN) are linked invariably to the innate immune response, particularly to the defence against bacterial infection. T lymphocytes are studied mainly in virus infections, the defence against tumours, the development and progression of chronic inflammatory processes, in autoimmune phenomena and in materno-fetal tolerance. There is, however, increasing evidence for communication and interactions between PMN and T cells that we discuss here in the context of different physiological and pathological conditions, including acute and chronic inflammatory disease, defence against tumours, and maint...
Source: Trends in Immunology - September 20, 2009 Category: Allergy & Immunology Authors: Müller I, Munder M, Kropf P, Hänsch GM Tags: Trends Immunol Source Type: journals

Esterases and autoimmunity: the sialic acid acetylesterase pathway and the regulation of peripheral B cell tolerance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The best studied mechanisms of B cell tolerance are receptor editing, clonal deletion and anergy. All of these mechanisms of B cell tolerance depend on the induction of signaling downstream of the B cell receptor by self-antigens. Another important and distinct mechanism of B cell tolerance involves the repression of antigen receptor signaling rather than its induction, utilizes the Lyn Src-family kinase, the SHP-1 tyrosine phosphatase, inhibitory members of the Siglec family, and a carbohydrate-modifying enzyme that is capable of negatively regulating B cell receptor activation known as sialic acid acetylesterase. ...
Source: Trends in Immunology - September 16, 2009 Category: Allergy & Immunology Authors: Pillai S, Cariappa A, Pirnie SP Tags: Trends Immunol Source Type: journals

How can a chemical element elicit complex immunopathology? Lessons from mercury-induced autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although most autoimmune diseases develop without a manifest cause, epidemiological studies indicate that external factors play an important role in triggering or aggravating autoimmune processes in genetically predisposed individuals. Nevertheless, most autoimmune disease-promoting environmental agents are unknown because their relationships to immune function are not understood. Thus, the study of animal models of chemically-induced autoimmunity should shed light on the pathways involved and allow us to identify these agents. The rodent model of heavy metal-induced autoimmunity is one of the most intriguing experimen...
Source: Trends in Immunology - August 23, 2009 Category: Allergy & Immunology Authors: Schiraldi M, Monestier M Tags: Trends Immunol Source Type: journals

An elegant defense: how neutrophils shape the immune response.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19709929 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - August 23, 2009 Category: Allergy & Immunology Authors: Soehnlein O Tags: Trends Immunol Source Type: journals

Alarmins link neutrophils and dendritic cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe here how alarmins released by neutrophil degranulation and/or death can link neutrophils to dendritic cells by promoting their recruitment and activation, resulting in the augmentation of innate and adaptive immune responses. PMID: 19699678 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - August 19, 2009 Category: Allergy & Immunology Authors: Yang D, de la Rosa G, Tewary P, Oppenheim JJ Tags: Trends Immunol Source Type: journals

The aryl hydrocarbon receptor in immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Low-molecular-weight chemicals or xenobiotics might contribute to the increasing prevalence of allergies and autoimmunity. Certain chemicals can alter immune responses via their action on the cytosolic transcription factor aryl hydrocarbon receptor (AhR). AhR recognizes numerous small xenobiotic and natural molecules, such as dioxin and the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole. Although AhR is best known for mediating dioxin toxicity, knockout studies have indicated that AhR also plays a role in normal physiology, including certain immune responses. In particular, Th17 cells and dendritic cells expres...
Source: Trends in Immunology - August 19, 2009 Category: Allergy & Immunology Authors: Esser C, Rannug A, Stockinger B Tags: Trends Immunol Source Type: journals

Lineage determination in haematopoiesis: Quo Vadis?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19699680 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - August 19, 2009 Category: Allergy & Immunology Authors: Brown G, Ceredig R Tags: Trends Immunol Source Type: journals

TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
TIR8, also known as single Ig IL-1 receptor (IL-R)-related molecule, SIGIRR, is a member of the IL-1R like (ILR) family. Unlike most other members of this family, it has a single extracellular Ig domain, a long cytoplasmic tail and a Toll/IL-1R (TIR) domain with two amino acid substitutions possibly consistent with non-conventional signaling. The TIR8 structure and pattern of expression are conserved in evolution from birds to humans. Current evidence suggests that TIR8 inhibits signaling receptor complexes of IL-1 family members associated with Th1 (IL-18), Th2 (IL-33) and Th17 (IL-1) differentiation. TIR8 also dampen...
Source: Trends in Immunology - August 19, 2009 Category: Allergy & Immunology Authors: Garlanda C, Anders HJ, Mantovani A Tags: Trends Immunol Source Type: journals

The ABC of dendritic cell development and function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
ATP-binding cassette (ABC) transporters are known for their involvement in clinical multidrug resistance (MDR) and their physiological defensive functions in barrier organs. More recently, attention has been focused on their possible involvement in the regulation of immune responses following the identification of their substrates as known immunomodulating agents (e.g. prostaglandins, leukotrienes and cyclic nucleotides) and their functional expression in various immune effector cells, most notably in dendritic cells (DCs). This review addresses the possible roles of ABC transporters in DC development and function, as ...
Source: Trends in Immunology - August 19, 2009 Category: Allergy & Immunology Authors: van de Ven R, Scheffer GL, Scheper RJ, de Gruijl TD Tags: Trends Immunol Source Type: journals

Neutrophil granule proteins tune monocytic cell function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Polymorphonuclear leukocytes (PMNs) release the contents of granules during their migration to inflammatory sites. On liberation from the first leukocyte to enter injured tissue, the granule proteins play a central role in the early inflammatory response. In particular, mononuclear phagocytes interact intimately with PMNs and their secretion products. PMN granule proteins enhance the adhesion of monocytes to the endothelium and stimulate subsequent extravasation of inflammatory monocytes. At the site of inflammation, PMN granule proteins activate macrophages to produce and release cytokines and to phagocytose IgG-opson...
Source: Trends in Immunology - August 19, 2009 Category: Allergy & Immunology Authors: Soehnlein O, Weber C, Lindbom L Tags: Trends Immunol Source Type: journals

NETs: a new strategy for using old weapons.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
As key players in the host innate immune response, neutrophils are recruited to sites of infection and constitute the first line of defense. They employ three strategies to eliminate invading microbes: microbial uptake, the secretion of antimicrobials, and the recently described release of Neutrophil Extracellular Traps (NETs). Composed of decondensed chromatin and antimicrobial proteins, NETs bind and kill a variety of microbes including bacteria, fungi, and parasites. In addition to using a repertoire of known antimicrobials, NETs incorporate histones into the antimicrobial arsenal. Furthermore, NETs may contribute t...
Source: Trends in Immunology - August 19, 2009 Category: Allergy & Immunology Authors: Papayannopoulos V, Zychlinsky A Tags: Trends Immunol Source Type: journals

Lymphocyte proliferation in immune-mediated diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Defects in T cell homeostatic mechanisms can result in T cell lymphopenia, defined as decreased numbers of lymphocytes. Lymphopenia results in homeostatic proliferation in order to maintain T cell homeostasis. It has been proposed that homeostatic proliferation can expand the pool of autoreactive T cells that promote autoimmunity, and indeed recent studies have further substantiated this observation in both animal models and humans. Conversely, homeostatic proliferation can promote tumor immunity by allowing tumor-specific T cells to accumulate. In this review, we discuss how the outcome of homeostatic proliferation ca...
Source: Trends in Immunology - August 18, 2009 Category: Allergy & Immunology Authors: Datta S, Sarvetnick N Tags: Trends Immunol Source Type: journals

Induction of autoimmunity by pristane and other naturally occurring hydrocarbons.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tetramethylpentadecane (TMPD, or commonly known as pristane)-induced lupus is a murine model of systemic lupus erythematosus (SLE). Renal disease and autoantibody production strictly depend on signaling through the interferon (IFN)-I receptor. The major source of IFN-I is immature monocytes bearing high levels of the surface marker Ly6C. Interferon production is mediated exclusively by signaling through TLR7 and the adapter protein MyD88. It is likely that endogenous TLR7 ligands such as components of small nuclear ribonucleoprotein complexes are involved in triggering disease. Lupus autoantibodies are produced in ecto...
Source: Trends in Immunology - August 18, 2009 Category: Allergy & Immunology Authors: Reeves WH, Lee PY, Weinstein JS, Satoh M, Lu L Tags: Trends Immunol Source Type: journals

The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nuclear factor (NF)-kappaB has an important role in immunity and inappropriate NF-kappaB activity has been linked with many autoimmune and inflammatory diseases. Multiple mechanisms normally ensure the proper termination of NF-kappaB activation. In this context, the intracellular ubiquitin-editing protein A20 (also known as Tumor Necrosis Factor Alpha-Induced Protein 3 or TNFAIP3) is a key player in the negative feedback regulation of NF-kappaB signaling in response to multiple stimuli. Moreover, A20 also regulates tumor necrosis factor (TNF)-induced apoptosis. Recent genetic studies demonstrate a clear association bet...
Source: Trends in Immunology - July 27, 2009 Category: Allergy & Immunology Authors: Vereecke L, Beyaert R, van Loo G Tags: Trends Immunol Source Type: journals

SOCS1 and SOCS3 in the control of CNS immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe CNS-relevant in vitro and in vivo studies that have examined the function of SOCS1 or SOCS3 under various neuroinflammatory or neuropathological conditions, including exposure of CNS cells to inflammatory cytokines or bacterial infection, demyelinating insults, stroke, spinal cord injury, multiple sclerosis and glioblastoma multiforme. PMID: 19643666 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - July 27, 2009 Category: Allergy & Immunology Authors: Baker BJ, Akhtar LN, Benveniste EN Tags: Trends Immunol Source Type: journals

Infections and autoimmunity - friends or foes?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autoimmunity can be triggered by many environmental factors, among which infectious agents are pivotal. Here, we summarize current knowledge of the relationship between infection and autoimmunity. An autoimmune disease can be induced or triggered by infectious agents, which can also determine its clinical manifestations. Most infectious agents, such as viruses, bacteria and parasites, can induce autoimmunity via different mechanisms. In many cases, it is not a single infection but rather the 'burden of infections' from childhood that is responsible for the induction of autoimmunity. The development of an autoimmune dis...
Source: Trends in Immunology - July 27, 2009 Category: Allergy & Immunology Authors: Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y Tags: Trends Immunol Source Type: journals

The role of environmental factors in primary biliary cirrhosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The etiology of primary biliary cirrhosis (PBC) is enigmatic, although it is clearly related to a combination of genetic predisposition and environmental stimulation. PBC is a chronic autoimmune cholestatic liver disease that occurs throughout the world with a reported latitudinal gradient in prevalence and incidence. PBC is also characterized by a 60% concordance in monozygotic twins and is considered a model autoimmune disease because of several features common to other conditions and the relatively homogeneous serological and biochemical features. Several risk factors have been suggested to be associated with PBC, i...
Source: Trends in Immunology - July 27, 2009 Category: Allergy & Immunology Authors: Selmi C, Gershwin ME Tags: Trends Immunol Source Type: journals

Novel insights into the biological function of mast cell carboxypeptidase A.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
When mast cells are activated they can respond by releasing their secretory granule compounds, including mast cell-specific proteases of chymase, tryptase and carboxypeptidase A (MC-CPA) type. MC-CPA is a dominant protein component of the mast cell granule and the MC-CPA gene is extremely highly expressed. Despite this, relatively little has been known of its biological function. However, the recent generation of mouse strains lacking MC-CPA has opened up new possibilities for investigations related to this protease. This recent development has revealed a role for MC-CPA in regulating innate immunity responses, includi...
Source: Trends in Immunology - July 27, 2009 Category: Allergy & Immunology Authors: Pejler G, Knight SD, Henningsson F, Wernersson S Tags: Trends Immunol Source Type: journals

Immune therapy for age-related diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human aging is reaching epidemic proportions as life expectancy increases and birth rate decreases. These demographic trends have led to a sharp increase in the diseases of aging, and an understanding of immune senescence promises to limit the development and progression of these diseases. In this review, we discuss three of the most important diseases of aging: shingles, Alzheimer's disease and atherosclerotic cardiovascular disease. All of these diseases have significant immunological components in either their etiology and/or progression, suggesting that appropriate immune intervention could be used in their prevent...
Source: Trends in Immunology - June 18, 2009 Category: Allergy & Immunology Authors: Weksler ME, Pawelec G, Franceschi C Tags: Trends Immunol Source Type: journals

Aging in the context of immunological architecture, function and disease outcomes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19541534 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - June 18, 2009 Category: Allergy & Immunology Authors: Dicarlo AL, Fuldner R, Kaminski J, Hodes R Tags: Trends Immunol Source Type: journals

Human innate immunosenescence: causes and consequences for immunity in old age.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The past decade has seen an explosion in research focusing on innate immunity. Through a wide range of mechanisms including phagocytosis, intracellular killing and activation of proinflammatory or antiviral cytokine production, the cells of the innate immune system initiate and support adaptive immunity. The effects of aging on innate immune responses remain incompletely understood, particularly in humans. Here we review advances in the study of human immunosenescence in the diverse cells of the innate immune system, including neutrophils, monocytes, macrophages, natural killer and natural killer T (NKT) cells and dend...
Source: Trends in Immunology - June 18, 2009 Category: Allergy & Immunology Authors: Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC Tags: Trends Immunol Source Type: journals

Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Aging affects every innate immune cell, including changes in cell numbers and function. Defects in the function of some cells are intrinsic, whereas for other cells, defects are extrinsic and possibly the consequence of the complex interactions with other cell types or the environmental milieu that is altered with aging. Abnormal function contributes to worsened outcomes after injury or infection and leads to diseases observed in the elderly. Knowing the mechanisms responsible for the aberrant function of innate immune cells might lead to the development of therapeutic strategies designed to improve innate immunity in ...
Source: Trends in Immunology - June 18, 2009 Category: Allergy & Immunology Authors: Kovacs EJ, Palmer JL, Fortin CF, Fülöp T, Goldstein DR, Linton PJ Tags: Trends Immunol Source Type: journals

T-cell immunosenescence: lessons learned from mouse models of aging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is well established that increasing age is associated with a decreased capacity of the immune system to mediate effective immune responses to vaccination and invading pathogens. Because of the inherent limitations of conducting experiments in humans, much of what we have learned is owed to the utility of experimental mouse models of aging. Recent studies performed in the mouse have demonstrated mechanisms responsible for age-related declines in the function of CD4(+) and CD8(+) cells. This review describes key findings regarding age-related defects in T-cell function and discusses the impact these defects have on va...
Source: Trends in Immunology - June 18, 2009 Category: Allergy & Immunology Authors: Maue AC, Yager EJ, Swain SL, Woodland DL, Blackman MA, Haynes L Tags: Trends Immunol Source Type: journals

An evolutionary perspective on the mechanisms of immunosenescence.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There is an accumulating body of evidence that a decline in immune function with age is common to most if not all vertebrates. For instance, age-associated thymic involution seems to occur in all species that possess a thymus, indicating that this process is evolutionary ancient and conserved. The precise mechanisms regulating immunosenescence remain to be resolved, but much of what we do know is consistent with modern evolutionary theory. In this review, we assess our current knowledge from an evolutionary perspective on the occurrence of immunosenescence, we show that life history trade-offs play a key role and we hi...
Source: Trends in Immunology - June 18, 2009 Category: Allergy & Immunology Authors: Shanley DP, Aw D, Manley NR, Palmer DB Tags: Trends Immunol Source Type: journals

Why does the thymus involute? A selection-based hypothesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Thymic involution remains a fundamental mystery in immunology. Here we present an argument that this seemingly counterproductive behavior may have evolved to allow for peripheral selection of a T-cell repertoire during young-adult life, optimized for fighting infections and avoiding reaction to self. Age-associated decline in immune function may be viewed as an unfortunate side effect of this selective process. Thus, the key to understanding thymic involution might lie in a more quantitative understanding of T-cell homeostasis in the periphery. PMID: 19540805 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - June 17, 2009 Category: Allergy & Immunology Authors: Dowling MR, Hodgkin PD Tags: Trends Immunol Source Type: journals

Aging in the lympho-hematopoietic stem cell compartment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cells of the immune system are progeny of a single primitive cell type, the hematopoietic stem cell (HSC). Aging in most strains of mice is associated with a reduction in HSC frequency and a reduction in HSC function. Aged HSCs demonstrate reduced differentiation toward the lymphoid lineage, and this might be a relevant factor influencing immunosenescence. The molecular mechanisms of HSC aging need to be determined in more detail, but current studies have identified, among others, a role for telomere dysfunction in inducing cell intrinsic checkpoints and environmental alterations, which both skews and reduces stem cell...
Source: Trends in Immunology - June 17, 2009 Category: Allergy & Immunology Authors: Geiger H, Rudolph KL Tags: Trends Immunol Source Type: journals

Thymic involution and immune reconstitution.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present here progress on the exploitation of thymosuppressive and thymostimulatory pathways using factors such as keratinocyte growth factor, interleukin 7 or sex steroid ablation for therapeutic thymus restoration and peripheral immune reconstitution in adults. PMID: 19540807 [PubMed - as supplied by publisher] (Source: Trends in Immunology)
Source: Trends in Immunology - June 17, 2009 Category: Allergy & Immunology Authors: Lynch HE, Goldberg GL, Chidgey A, Van den Brink MR, Boyd R, Sempowski GD Tags: Trends Immunol Source Type: journals

Vaccination in the elderly: an immunological perspective.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Successful vaccination of the elderly against important infectious pathogens that cause high morbidity and mortality represents a growing public health priority. Building on the theme of aging and immunosenescence, we review mechanisms of human immunosenescence and the immune response to currently licensed vaccines. We discuss the difficulties in identifying the risk factors that, in addition to aging, cause immunosenescence and address the relative paucity of vaccine studies in the elderly. We conclude that vaccine responses are blunted in the elderly compared with that of healthy young adults. However, it is also cle...
Source: Trends in Immunology - June 17, 2009 Category: Allergy & Immunology Authors: Chen WH, Kozlovsky BF, Effros RB, Grubeck-Loebenstein B, Edelman R, Sztein MB Tags: Trends Immunol Source Type: journals

CD28(-) T cells: their role in the age-associated decline of immune function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The accumulation of CD28(-) T cells, particularly within the CD8 subset, is one of the most prominent changes during T-cell homeostasis and function associated with aging in humans. CD28, a major co-stimulatory receptor, is responsible for the optimal antigen-mediated T-cell activation, proliferation and survival of T cells. CD28(-) T cells exhibit reduced antigen receptor diversity, defective antigen-induced proliferation and a shorter replicative lifespan while showing enhanced cytotoxicity and regulatory functions. Gene expression analyses reveal profound changes of CD28(-) T cells in comparison to their CD28(+) cou...
Source: Trends in Immunology - June 17, 2009 Category: Allergy & Immunology Authors: Weng NP, Akbar AN, Goronzy J Tags: Trends Immunol Source Type: journals

B cells and aging: molecules and mechanisms.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent advances allow aging-associated changes in B-cell function to be approached at a mechanistic level. Reduced expression of genes crucial to lineage commitment and differentiation yield diminished B-cell production. Moreover, intrinsic differences in the repertoire generated by B-cell precursors in aged individuals, coupled with falling B-cell generation rates and life-long homeostatic competition, result in narrowed clonotypic diversity. Similarly, reductions in gene products crucial for immunoglobulin class switch recombination and somatic hypermutation impact the efficacy of humoral immune responses. Together, ...
Source: Trends in Immunology - June 17, 2009 Category: Allergy & Immunology Authors: Cancro MP, Hao Y, Scholz JL, Riley RL, Frasca D, Dunn-Walters DK, Blomberg BB Tags: Trends Immunol Source Type: journals

Mucosal immunosenescence: new developments and vaccines to control infectious diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Infection of the aero-digestive tract represents a major disease burden of the elderly, and despite recent advances in our understanding of the mucosal immune system, its immunosenescence remains poorly defined. Age-associated alterations of the intestinal and respiratory immune systems occur at distinct times and in a distinct manner. A reduction in gut-associated lymphoreticular tissues, intestinal antigen-specific IgA antibody responses and lack of oral tolerance induction are all associated with aging. By contrast, nasopharyngeal-associated lymphoreticular tissue function remains intact during aging with notable si...
Source: Trends in Immunology - June 17, 2009 Category: Allergy & Immunology Authors: Fujihashi K, Kiyono H Tags: Trends Immunol Source Type: journals

Neurokinin 1 receptor isoforms and the control of innate immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Substance P is the prototype tachykinin peptide and triggers a variety of biological effects in both the nervous and immune system. Two naturally occurring variants of the neurokinin 1 receptor (NK1R) mediate the effects of SP: a 'classic' full-length receptor and a truncated (tail-less) form that lacks 96 amino acid residues at the C-terminus. Most research has focused on the full length receptor and the truncated NK1R has not been extensively explored. Recent data demonstrate that truncated NK1R has important functional roles, including modulation of responses triggered by cytokines, chemotaxis of macrophages and reg...
Source: Trends in Immunology - May 31, 2009 Category: Allergy & Immunology Authors: Tuluc F, Lai JP, Kilpatrick LE, Evans DL, Douglas SD Tags: Trends Immunol Source Type: journals

A(2B) adenosine receptors in immunity and inflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A(2B) adenosine receptors are increasingly recognized as important orchestrators of inflammation. A(2B) receptor activation promotes the inflammatory response of mast cells, epithelial cells, smooth muscle cells and fibroblasts, thereby contributing to the pathophysiology of asthma and colitis. A(2B) receptor stimulation limits endothelial cell inflammatory responses and permeability and suppresses macrophage activation thereby preventing tissue injury after episodes of hypoxia and ischemia. A(2B) receptor stimulation also promotes the production of angiogenic cytokines by endothelial cells, mast cells and dendritic ce...
Source: Trends in Immunology - May 31, 2009 Category: Allergy & Immunology Authors: Haskó G, Csóka B, Németh ZH, Vizi ES, Pacher P Tags: Trends Immunol Source Type: journals

EBV in MS: guilty by association?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Epstein-Barr Virus (EBV) is one of the most successful human viruses, infecting more than 90% of the adult population worldwide and persisting for the lifetime of the host. Individuals with a history of symptomatic primary EBV infection, called infectious mononucleosis, carry a moderately higher risk of developing multiple sclerosis (MS). In addition, EBV-specific immune responses, which crucially regulate the host-virus balance in healthy virus carriers, are altered in patients with MS. Although no data so far unequivocally support a direct etiologic role of the virus, recent studies allow for the development of testa...
Source: Trends in Immunology - May 31, 2009 Category: Allergy & Immunology Authors: Lünemann JD, Münz C Tags: Trends Immunol Source Type: journals

Enabling a systems biology approach to immunology: focus on innate immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Immunity is not simply the product of a series of discrete linear signalling pathways; rather it is comprised of a complex set of integrated responses arising from a dynamic network of thousands of molecules subject to multiple influences. Its behaviour often cannot be explained or predicted solely by examining its components. Here, we review recently developed resources for the systems-level investigation of immunity. Although innate immunity is emphasized here, its considerable overlap with adaptive immunity makes many of these resources relevant to both arms of the immune response. We discuss recent studies implemen...
Source: Trends in Immunology - May 31, 2009 Category: Allergy & Immunology Authors: Gardy JL, Lynn DJ, Brinkman FS, Hancock RE Tags: Trends Immunol Source Type: journals